Protocolo de actuación en el tratamiento odontológicoquirúrgico en pacientes con angioedema hereditario. Revisión de la literatura / Management protocol of dental treatment in patients with hereditary angioedema. A literature review

El angioedema hereditario (AEH) es una enfermedad genética rara de transmisión autosómica dominante, en la que existe un déficit de la encima C1-INH. Cursa con episodios recurrentes y autolimitados de edema, causados por aumento de la permeabilidad vascular. Tiene unas importantes implicaciones para los profesionales de la salud bucodental, ya que determinados procedimientos odontológicos y quirúrgicos pueden desencadenar episodios de angioedema, potencialmente mortales al producirse edema en las vías respiratorias superiores. El objetivo de este trabajo es aportar información y recomendaciones a los odontólogos a la hora de tratar a estos pacientes con el fin de minimizar las complicaciones. Los resultados han aportado un total de 48 pacientes y se realizaron un total de 90 intervenciones, siendo el tratamiento más frecuente las extracciones dentales. El AEH tipo I es el más frecuente de los tres tipos con una incidencia de entorno al 85% y el tipo III es el menos común y conocido, ya que se ha identificado en los últimos años. La profilaxis a corto plazo es un método preventivo que ha de realizarse en todos los pacientes con AEH antes de cualquier intervención quirúrgica odontológica. El tratamiento de estos pacientes implica, en la mayoría de las ocasiones, una profilaxis a largo y corto plazo con el fin de disminuir los ataques. Siendo aconsejable realizar los procedimientos odontológicos-quirúrgicos en ambiente hospitalario

Hereditary angioedema (HAE) is a rare genetic disease of autosomal dominant transmission, in which there is a deficit of C1-INH enzyme. It runs with recurrent and self-limited episodes of edema to increase vascular permeability. There are some important complications for oral health professionals because many dental and surgical procedures can trigger angioedema episodes which can be a potentially life-threating condition due to edema in the upper respiratory tract. The objective of this research is to provide information and recommendations to dentists for treating these patients in order to minimize complications. 48 patients have been reported and a total of 90 interventions were performed, being extractions the most frequent treatment. HAE type 1 is the most frequent of the three types with an 85% of incidence, and type III is the least common and known, it has been identified in recent years. Shortterm prophylaxis is a preventive method that must be done in all HAE patients before any dental surgery. The treatment of these patients implies, in most cases, a long- and short-term prophylaxis in order to reduce attacks. It is recommended to realize dental-surgical procedures in a hospital environment

Enfermedad de Morquio en un niño / Morquio disease in a child

Se presenta el caso clínico de un niño de 8 años de edad, con antecedentes de infecciones respiratorias repetidas, atendido en el centro de salud de Archidona hacía 4 años, y desde aquí fue remitido hacia el hospital de la ciudad de Tena, donde le indicaron algunos exámenes complementarios que no concluyeron el diagnóstico. Posteriormente fue trasladado al Hospital Pediátrico Baca Ortiz y los resultados de los exámenes efectuados, como pruebas enzimáticas y el análisis cromosómico o cariotipo, confirmaron el diagnóstico de enfermedad de Morquio. Se dieron orientaciones generales, se indicó tratamiento sintomático y fisioterapia en el área de salud; asimismo, se brindó asesoramiento genético a la madre(AU)

The case report of an 8 years boy with history of repeated breathing infections is presented. He was assisted 4 years ago in the health center of Archidona, and he was referred to the hospital of Tena city, where some complementary exams that didn't conclude the diagnosis were indicated. Later on he was transferred to Baca Ortiz Pediatric Hospital and the results of the exams, as enzymatic tests and the chromosomal analysis or cariotype, confirmed the diagnosis of Morquio disease. Some general orientations were given, symptomatic treatment and physiotherapy in the health area was indicated; also, a genetic advice was offered to the mother(AU)

Enfermedad de Morquio en un niño / Morquio disease in a child

Se presenta el caso clínico de un niño de 8 años de edad, con antecedentes de infecciones respiratorias repetidas, atendido en el centro de salud de Archidona hacía 4 años, y desde aquí fue remitido hacia el hospital de la ciudad de Tena, donde le indicaron algunos exámenes complementarios que no concluyeron el diagnóstico. Posteriormente fue trasladado al Hospital Pediátrico Baca Ortiz y los resultados de los exámenes efectuados, como pruebas enzimáticas y el análisis cromosómico o cariotipo, confirmaron el diagnóstico de enfermedad de Morquio. Se dieron orientaciones generales, se indicó tratamiento sintomático y fisioterapia en el área de salud; asimismo, se brindó asesoramiento genético a la madre

The case report of an 8 years boy with history of repeated breathing infections is presented. He was assisted 4 years ago in the health center of Archidona, and he was referred to the hospital of Tena city, where some complementary exams that didn't conclude the diagnosis were indicated. Later on he was transferred to Baca Ortiz Pediatric Hospital and the results of the exams, as enzymatic tests and the chromosomal analysis or cariotype, confirmed the diagnosis of Morquio disease. Some general orientations were given, symptomatic treatment and physiotherapy in the health area was indicated; also, a genetic advice was offered to the mother

Signos de alarma en las enfermedades metabólicas hereditarias / Warning signs in hereditary metabolic diseases

La mayoría de las enfermedades metabólicas se debe a una deficiencia enzimática en alguna de las numerosas vías metabólicas derivadas de los carbohidratos, las proteínas o los ácidos grasos, o del tráfico intracelular. Se manifiestan en cualquier momento de la vida, sobre todo en el periodo neonatal, pero también pueden hacerlo en la infancia o edad adulta. Aunque todavía no se diagnostican de forma suficiente, en los últimos años el campo de los errores innatos del metabolismo (EIM) ha evolucionado desde lo que constituía un grupo limitado de enfermedades raras (ER), poco frecuentes, desconocidas y a menudo fatales, hacia una serie de enfermedades graves pero tratables. Dadas la diversidad y la baja frecuencia de cada uno de los EIM, su seguimiento se realiza habitualmente en centros de referencia, pero en todos los demás escalones asistenciales deben poder iniciarse investigaciones y/o tratamientos antes de referir al paciente. Los responsables de la atención de pacientes afectos de un EIM deben conocer las características básicas de cada enfermedad, los alimentos permitidos y prohibidos, las posibles complicaciones y cómo actuar ante descompensaciones agudas a las que idealmente debieran anticiparse

Most metabolic diseases are due to an enzymatic deficiency in one of the numerous metabolic pathways derived from carbohydrates, proteins or fatty acids, or from intracellular trafficking. They manifest at any time in life, especially in the neonatal period, but they can also do so in childhood or adulthood. Although not yet sufficiently diagnosed, in recent years the field of inborn errors of metabolism (EIM) has evolved from what constituted a limited group of rare, unknown and often fatal diseases to a series of serious but treatable diseases. Given the diversity and low frequency of each of the EIM, their follow-up is usually done in reference centers, but in all other levels of care should be able to initiate research and / or treatments before referring the patient. Those responsible for the care of patients affected by an EIM must know the basic characteristics of each disease, the permitted and forbidden food, the possible complications and how to act in the face of acute descompensation to which they should ideally anticipate

Exchange of Partial Liver Transplantation Between Children with Different Non-Cirrhotic Metabolic Liver Diseases: How Do We Arrive There?

Hepatic-based metabolic disorders are characterized by an enzyme deficiency expressed solely or mainly in the liver. They are divided into cirrhotic or non-cirrhotic metabolic liver diseases (NCMLDs), and most of them can be treated by liver transplantation. Because the livers with NCMLDs are usually structurally and functionally normal, the primary aim of the liver graft is to support the deficient enzymes rather than maintaining liver functions. Hence, we hypothesize that the exchange of partial liver grafts by the technique of auxiliary partial orthotopic liver transplantation (APOLT) between patients with 2 different NCMLDs may be feasible to replace the deficient enzymes in each patient. This hypothesis is based on the following conditions: (i) the patients have no chance of undergoing timely liver transplantation, (ii) the symptoms of each NCMLD may be alleviated after exchanging partial liver grafts, and (iii) each graft is anatomically appropriate for APOLT. In addition, we evaluate it with a focus on selection of cases, designing of graft sizes, and surgical techniques for reciprocal APOLT.

[Food intolerances caused by enzyme defects and carbohydrate malassimiliations : Lactose intolerance and Co]. / Lebensmittelunverträglichkeiten durch Enzymdefekte und Zuckerverwertungsstörungen : Laktoseintoleranz und Co.

Apart from allergic conditions, carbohydrate malassimiliations (sugar metabolism disorders) are classified within the group of food intolerances. These dose-dependent, yet non-immunological reactions require gastroenterological or internal diagnosis following nutritional therapy. Intolerances to carbohydrates such as lactose (milk sugar) and fructose (fruit sugar) in addition to sugar alcohols (sorbitol, mannitol, lactitol etc.) have been gaining increasing attention in recent decades as they are the cause of a wide range of gastrointestinal symptoms. There are currently various options for both diagnosis and therapy that differ notably in terms of effort, costs, and efficiency. Nutritional change and patient education are the bases of therapy. Non-observance of the trigger will result in increasing complaints and possibly even more infections, e.g., diverticula, rectal disorders, bacterial miscolonization, bile acid malabsorption). For an optimal therapy, the following sugar metabolism disorders have to be differentiated: hypolactasia versus lactose maldigestion, fructose malabsorption versus fructose overload, combined lactose and fructose intolerance, and isolated adverse reactions against sorbitol.For the medical conditions listed above, a three- or four-stage treatment regimen is recommended. Extensive dietary restrictions with regard to the relevant sugar, except for lactose, should not be maintained over a longer period of time.

La porfiria: no solo la histeria es una gran simuladora / Porphyria: not only the hysteria is a great imitator

Las porfirias son enfermedades caracterizadas por la acumulación de porfirinas y precursores de porfirina debido a deficiencias enzimáticas en la síntesis del grupo hemo. Esta enfermedad simula una amplia variedad de trastornos, dada la multitud de síntomas con la que se puede presentar, y por lo tanto plantea grandes dificultades diagnósticas. Se presenta un caso en el que la existencia de síntomas psiquiátricos se vio empañada por la presencia de otros síntomas clásicos de la porfiria. Hay un alto riesgo vital en los pacientes afectos de porfiria, tanto por el infradiagnóstico como por la variedad de síntomas que presentan que pueden enmascarar algunos tan severos como una psicosis (AU)

The porphyrias are diseases characterised by accumulation of porphyrins and porphyrin precursors due to enzymatic deficiencies of the haem-synthesis pathaway. It mimics a variety of disorders and thus poses a diagnostic quagmire. A case is reported in which the presence of psychiatric symptoms was masked by the presence of other classic symptoms of porphyria. There is a vital risk in patients with porphyria, due to underdiagnosis presented, as well as the variety of symptoms that arise that may mask some as severe as psychosis (AU)

Confirmación genética del déficit de mioadenilato desaminasa / Genetic confirmation of myoadenylate deaminase deficiency

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HMBPP-deficient Listeria mutant immunization alters pulmonary/systemic responses, effector functions, and memory polarization of Vγ2Vδ2 T cells.

Whereas infection or immunization of humans/primates with microbes coproducing HMBPP/IPP can remarkably activate Vγ2Vδ2 T cells, in vivo studies have not been done to dissect HMBPP- and IPP-driven expansion, pulmonary trafficking, effector functions, and memory polarization of Vγ2Vδ2 T cells. We define these phosphoantigen-host interplays by comparative immunizations of macaques with the HMBPP/IPP-coproducing Listeria ΔactA prfA* and HMBPP-deficient Listeria ΔactA ΔGCPE: prfA* mutant. The HMBPP-deficient ΔGCPE: mutant shows lower ability to expand Vγ2Vδ2 T cells in vitro than the parental HMBPP-producing strain but displays comparably attenuated infectivity or immunogenicity. Respiratory immunization of macaques with the HMBPP-deficient mutant elicits lower pulmonary and systemic responses of Vγ2Vδ2 T cells compared with the HMBPP-producing vaccine strain. Interestingly, HMBPP-deficient mutant reimmunization or boosting elicits enhanced responses of Vγ2Vδ2 T cells, but the magnitude is lower than that by HMBPP-producing listeria. HMBPP-deficient listeria differentiated fewer Vγ2Vδ2 T effector cells capable of coproducing IFN-γ and TNF-α and inhibiting intracellular listeria than HMBPP-producing listeria. Furthermore, HMBPP deficiency in listerial immunization influences memory polarization of Vγ2Vδ2 T cells. Thus, both HMBPP and IPP production in listerial immunization or infection elicit systemic/pulmonary responses and differentiation of Vγ2Vδ2 T cells, but a role for HMBPP is more dominant. Findings may help devise immune intervention.

Mucopolysaccharide diseases: a complex interplay between neuroinflammation, microglial activation and adaptive immunity.

Mucopolysaccharide (MPS) diseases are lysosomal storage disorders (LSDs) caused by deficiencies in enzymes required for glycosaminoglycan (GAG) catabolism. Mucopolysaccharidosis I (MPS I), MPS IIIA, MPS IIIB and MPS VII are deficient in the enzymes α-L-Iduronidase, Heparan-N-Sulphatase, N-Acetylglucosaminidase and Beta-Glucuronidase, respectively. Enzyme deficiency leads to the progressive multi-systemic build-up of heparan sulphate (HS) and dermatan sulphate (DS) within cellular lysosomes, followed by cell, tissue and organ damage and in particular neurodegeneration. Clinical manifestations of MPS are well established; however as lysosomes represent vital components of immune cells, it follows that lysosomal accumulation of GAGs could affect diverse immune functions and therefore influence disease pathogenesis. Theoretically, MPS neurodegeneration and GAGs could be substantiating a threat of danger and damage to alert the immune system for cellular clearance, which due to the progressive nature of MPS storage would propagate disease pathogenesis. Innate immunity appears to have a key role in MPS; however the extent of adaptive immune involvement remains to be elucidated. The current literature suggests a complex interplay between neuroinflammation, microglial activation and adaptive immunity in MPS disease.

Cell-specific in vivo functions of glycosphingolipids: lessons from genetic deletions of enzymes involved in glycosphingolipid synthesis.

Glycosphingolipids (GSLs) are believed to be involved in many cellular events including trafficking, signaling and cellular interactions. Over the past decade considerable progress was made elucidating the function of GSLs by generating and exploring animal models with GSL-deficiency. Initial studies focused on exploring the role of complex sialic acid containing GSLs (gangliosides) in neuronal tissue. Although complex gangliosides were absent, surprisingly, the phenotype observed was rather mild. In subsequent studies, several mouse models with combinations of gene-deletions encoding GSL-synthesizing enzymes were developed. The results indicated that reduction of GSL-complexity correlated with severity of phenotypes. However, in these mice, accumulation of precursor GSLs or neobiosynthesized GSL-series seemed to partly compensate the loss of GSLs. Thus, UDP-glucose:ceramide glucosyltransferase (Ugcg), catalyzing the basic step of the glucosylceramide-based GSL-biosynthesis, was genetically disrupted. A total systemic deletion of Ugcg caused early embryonic lethality. Therefore, Ugcg was eliminated in a cell-specific manner using the cre/loxP-system. New insights into the cellular function of GSLs were gained. It was demonstrated that neurons require GSLs for differentiation and maintenance. In keratinocytes, preservation of the skin barrier depends on GSL synthesis and in enterocytes of the small intestine GSLs are involved in endocytosis and vesicular transport.

[Inherited disorders of liver metabolism]. / Hereditäre Lebererkrankungen.

Inherited disorders of liver metabolism are in general due to single enzyme defects that result in abnormalities in the synthesis or catabolism of proteins, carbohydrates, or lipids. This group of diseases comprises disorders of the amino acid, iron, bilirubin and sphingolipid metabolism as well as disorders of the coagulation cascade, the urea cycle and diverse transport processes. These diseases either lead to structural liver damage or, if the defective enzyme is produced predominantly in the liver, to injury to other organ systems. In this review article, we discuss the pathogenesis, clinical presentation, diagnosis and therapy of hereditary hemochromatosis, Wilson's disease and alpha1-antitrypsin-deficiency which represent the most common hereditary liver diseases.

Propiedades antioxidantes y antiinflamatorias de las lipoproteínas de alta densidad / Antioxidant and antiinflammatory properties of high-density lipoproteins

Más allá del papel en el transporte reverso de colesterol de las lipoproteínas de alta densidad (HDL), en la última década se han descrito nuevos mecanismos antiaterogénicos de las HDL. Dos de estos mecanismos, estrechamente relacionados, son la capacidad de las HDL para prevenir la oxidación de las lipoproteínas de baja densidad (LDL) y su actividad antiinflamatoria. Algunas propiedades antiinflamatorias de la HDL son mediadas por el contenido en algunos lípidos, como el colesterol no esterificado o la esfingosina-1- fosfato; sin embargo, la principal actividad antiinflamatoria de las HDL la ejercen las apolipoproteínas (apo) y enzimas asociadas. Proteínas como apo A-I, proteína transferidora de ésteres de colesterol, paraoxonasa, acetilhidrolasa del factor activador plaquetario y apo J actúan coordinadamente para transferir los peróxidos lipídicos, potentes agentes oxidantes, desde las LDL oxidadas hasta las HDL, captarlos y degradarlos generando productos no inflamatorios. El contenido relativo de estas proteínas en las diferentes subfracciones de HDL determina el potencial antiinflamatorio de cada subfracción (AU)

In addition to the role of high-density lipoproteins (HDL) in reverse cholesterol transport, new antiatherogenic mechanisms of HDL have been described in the last 10 years. Two of these mechanisms, which are closely related, are the ability of HDL to prevent lowdensity lipoprotein (LDL) oxidation and its antiinflammatory activity. Some of the antiinflammatory properties of HDL are mediated by the content in some lipids such as non-esterified cholesterol or sphingosin-1-phosphate; however, the main antiinflammatory activity of HDL is exerted by the apolipoproteins (apo) and their associated enzymes. Proteins such as apoA-I, cholesteryl ester transfer protein (CETP), paraoxonase, platelet activator favor-acetylhydrolase (PAF-AH) and apoJ act in a coordinated fashion to transfer lipid peroxides, potent oxidizing agents, ranging from oxidized LDLs to HDLs, capture and degrade these lipid peroxides, generating non-inflammatory products. The relative content of these proteins in the distinct HDL subfractions determines the antiinflammatory potential of each subfraction (AU)

¿Son todas las partículas de lipoproteínas de alta densidad iguales? / Are all high-density lipoprotein particles equal?

El análisis de las modificaciones de genes que influencian el metabolismo y la función de las lipoproteínas de alta densidad (HDL) en modelos murinos, demuestra que los cambios (aumentos o disminución) de colesterol unido a HDL no son un predictor adecuado de la susceptibilidad a la arteriosclerosis de éstos. Por tanto, los diferentes tipos de partículas de HDL generados por intervención sobre distintas potenciales dianas terapéuticas no son iguales en cuanto a su potencial antiaterogénico. El análisis del transporte reverso de colesterol específico de macrófagos, y de la capacidad de las HDL de proteger frente a la modificación oxidativa de lipoproteínas de baja densidad, aporta una mejor predicción del efecto de la modificación genética efectuada sobre la susceptibilidad a la arteriosclerosis (AU)

Analysis of the genetic modifications that influence high-density lipoprotein (HDL) metabolism and function in murine models shows that changes (whether increases or decreases) in HDL-cholesterol do not accurately predict susceptibility to arteriosclerosis in these models. Therefore, the distinct types of HDL particles generated by interventions on the various potential therapeutic targets differ in their antiatherogenic potential. Analysis of macrophage-specific reverse cholesterol transport and the ability of HDL to protect LDL against oxidative modification is better able to predict the effect of genetic modification on susceptibility to arteriosclerosis (AU)

Torcetrapib: una perspectiva histórica / Torcetrapib: a historical view

Diversos estudios experimentales han demostrado que las lipoproteínas de alta densidad (HDL) representan un grupo funcionalmente muy heterogéneo de partículas con diversos efectos antioxidantes, antiinflamatorios, que les confiere propiedades antiaterogénicas y antitrombóticas. En la actualidad, se dispone de potentes alternativas terapéuticas que permiten alcanzar cifras muy bajas de colesterol unido a lipoproteínas de baja densidad, y desde hace varios años están en continuo desarrollo y evaluación fármacos que permiten incrementos significativos de los valores de colesterol unido a HDL, con la intención de mejorar el perfil cardiovascular de los pacientes. Los inhibidores de la enzima colesterol- éster transferasa constituyen una opción terapéutica válida para este fin. A continuación se revisan los resultados de los primeros y principales ensayos clínicos que evalúan la eficacia de uno de estos fármacos (torcetrapib) así como los análisis pormenorizados realizados posteriormente por sus principales autores de las posibles explicaciones de los resultados clínicos desfavorables de éstos (AU)

Several experimental studies have shown that high-density lipoproteins are functionally a highly heterogeneous group of particles with varied antioxidant and antiinflammatory effects, conferring them with antiatherogenic and antithrombotic properties. Potent therapeutic alternatives are currently available that allow very low values of low-density lipoprotein to be achieved. For several years, drugs that allow significant increases in high-density lipoprotein cholesterol levels have been under continuous development and evaluation, with the aim of improving patients’ cardiovascular profiles. Cholesteryl ester transfer protein inhibitors are a suitable therapeutic option for this aim. We review the results of the first and main clinical trials evaluating the efficacy of one of these drugs (torcetrapib) as well as the detailed analyses subsequently performed by their main authors of the possible explanations for the unfavorable clinical results of these trials (AU)

Transcellular biosynthesis of cysteinyl leukotrienes in vivo during mouse peritoneal inflammation.

Leukotrienes (LTs) are lipid mediators of inflammation formed by enzymatic oxidation of arachidonic acid. One intriguing aspect of LT production is transcellular biosynthesis: cells expressing 5-lipoxygenase (5LO) form LTA(4) and transfer it to cells expressing LTA(4) hydrolase (LTA(4)H) or LTC(4) synthase (LTC(4)S) to produce LTB(4) or LTC(4). This process has been demonstrated in vivo for LTB(4), but not for cysteinyl LTs (cysLTs). We examined transcellular cysLT synthesis during zymosan-induced peritonitis, using bone marrow transplants with transgenic mice deficient in key enzymes of LT synthesis and analyzing all eicosanoids by liquid chromatography/tandem mass spectrometry. WT mice time-dependently produced LTB(4) and cysLTs (LTC(4), LTD(4), and LTE(4)). 5LO(-/-) mice were incapable of producing LTs. WT bone marrow cells restored this biosynthetic ability, but 5LO(-/-) bone marrow did not rescue LT synthesis in irradiated WT mice, demonstrating that bone marrow-derived cells are the ultimate source of all LTs in this model. Total levels of 5LO-derived products were comparable in LTA(4)H(-/-) and WT mice, but were reduced in LTC(4)S(-/-) animals. No differences in prostaglandin production were observed between these transgenic or chimeric mice. Bone marrow cells from LTA(4)H(-/-) or LTC(4)S(-/-) mice injected into 5LO(-/-) mice restored the ability to synthesize LTB(4) and cysLTs, providing unequivocal evidence of efficient transcellular biosynthesis of cysLTs. These results highlight the potential relevance of transcellular exchange of LTA(4) for the synthesis of LTs mediating biological activities during inflammatory events in vivo.

Fast-twitch sarcomeric and glycolytic enzyme protein loss in inclusion body myositis.

Inclusion body myositis (IBM) is an inflammatory disease of skeletal muscle of unknown cause. To further understand the nature of the tissue injury in this disease, we developed methods for large-scale detection and quantitation of proteins in muscle biopsy samples and analyzed proteomic data produced by these methods together with histochemical, immunohistochemical, and microarray data. Twenty muscle biopsy samples from patients with inflammatory myopathies (n = 17) or elderly subjects without neuromuscular disease (n = 3) were profiled by proteomic studies using liquid chromatographic separation of peptides followed by mass spectrometry. Thirteen of the diseased samples additionally underwent microarray studies. Seventy muscle specimens from patients with a range of neuromuscular disorders were examined by ATPase histochemical methods. Smaller numbers of samples underwent immunohistochemical and immunoblot studies. Mass spectrometric studies identified and quantified approximately 300 total distinct proteins in each muscle sample. In IBM and to a lesser extent in polymyositis, proteomic studies confirmed by histochemical, immunohistochemical, and immunoblot studies showed loss of many fast-twitch specific structural proteins and glycolytic enzymes despite relative preservation of transcript levels. Increased abundance of a nuclear membrane protein, immunoglobulins, and two calpain-3 substrates were present. The atrophy present in IBM muscle is accompanied by preferential loss of fast-twitch structural proteins and glycolytic enzymes, particularly glycogen debranching enzyme, with relative preservation of the abundance of their respective transcripts. Although muscle atrophy has long been recognized in IBM, these studies are the first to report specific proteins which are reduced in quantity in IBM muscle.

ERGs in children with pancreatic enzyme insufficient and pancreatic enzyme sufficient cystic fibrosis.

OBJECTIVES: We recorded scotopic and photopic flash electroretinograms (ERGs) in pediatric subjects with cystic fibrosis, aged 4 to 18 years, who were either pancreatic insufficient (PI) or pancreatic sufficient (PS). The aim of the study was to determine whether vitamin supplementation in the PI group allowed comparable retinal function in these two groups. METHODS: ERGs were recorded from a mixed-gender group of 41 children and adolescents (4 to 17 years of age) with cystic fibrosis. The subjects were grouped according to pancreatic function into PI (n = 29) and PS (n = 12). Full-field flash ERGs were recorded from one eye using a DTL fiber. The pupil was dilated prior to recording using two drops of 0.5% tropicamide. ISCEV photopic and scotopic stimuli and recording conditions were used. Serum levels of vitamin A, beta carotene and retinol binding protein (RBP) were measured on the day of ERG recording. RESULTS: There was no significant difference in ERG amplitudes or implicit times between PI and PS groups. Vitamin A, beta carotene, and RBP levels were not significantly different across the two groups and were not correlated with implicit times or amplitudes of any of the ERG types recorded here. CONCLUSION: Similarity of ERGs across the PI and PS cystic fibrosis patient populations tested here suggests that the supplementation protocol applied to these populations allows similar levels of retinal function (as indicated by flash ERG parameters) in the two groups.

Musculoskeletal complications encountered in the lysosomal storage disorders.

The lysosomal storage disorders are a heterogeneous group of inherited metabolic diseases resulting from defects in the degradation or transport of several distinct by-products of cellular turnover. The various subtypes are characterized by multi-systemic involvement; the wide range in patient ages at symptom onset is only partly explained by the underlying mutation(s). Neurodegenerative features and musculoskeletal complications are often seen in the most severe variants, and are features of the disease that have the most significant impact on patients' physical and functional well-being. Until recently, the care of affected individuals relied mainly on palliative or supportive measures. The introduction of therapies directed at correcting the primary defect (i.e., deficient enzyme activity) in several of these disorders has led to modification of the phenotype and natural history or disease course; however, clinical problems arising from brain and bone involvement remain major sources of morbidity. Factors that might influence therapeutic outcome include pre-existing pathology at the time of treatment initiation, drug access to tissues sites of pathology, and - in the case of enzyme therapy - antibody formation. Increasing understanding of the pathogenesis or relevant mechanism(s) of diseases is providing insights into additional therapeutic targets, enabling the potential for optimized patient outcomes with the use of adjunctive or supplemental agents. Physical and occupational therapy remain critical components of a comprehensive approach to patient care.